Functional characterization of CDK10 and cyclin M truncated variants causing severe developmental disorders.

ABSTRACT:

Background

CDK10 is a poorly known cyclin M (CycM)-dependent kinase. Loss-of-function mutations in the genes encoding CycM or CDK10 cause, respectively, STAR or Al Kaissi syndromes, which present a constellation of malformations and dysfunctions. Most reported mutations abolish gene expression, but two mutations found in 3' exons could allow the expression of CDK10 and CycM truncated variants.

Methods

We built a structural model that predicted a preserved ability of both variants to form a CDK10/CycM heterodimer. Hence, we functionally characterized these two truncated variants by determining their capacity to heterodimerize and form an active protein kinase when expressed in insect cells, by examining their two-hybrid interaction profiles when expressed in yeast, and by obs

SUBMITTER: Robert T 

PROVIDER: S-EPMC8580092 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature